Category: medications

I’ve written in the past about the use of a pharmaceutical version of the drug ketamine (known as the party drug, “Special K”) in studies with depression and with bipolar disorder. Recently, I learned researchers have published a new study looking at the impact of ketamine on obsessive compulsive disorder (OCD).

I was on the phone with someone interested in OCD treatment, and she mentioned she had read some promising work at Yale about an experimental treatment that involved increasing glutamate levels in people with OCD. Glutamate is a neurotransmitter in the brain. Ketamine affects NMDA, an important receptor for glutamate, leading to lower levels of glutamate in the brain. I told the caller I wasn’t familiar with this line of research, and she kindly sent me a few links, including the one below.

The IOCDF article
The International OCD Foundation (IOCDF) has an article on their website about the potential role of glutamate in understanding OCD, under the subheading, “Cutting Edge Research on New Medication Options.” It’s written by three doctors associated with Yale University. The authors summarize some research finding higher levels of glutamate in the brain in people with OCD. Although they acknowledge important caveats about what is known about glutamate so far, the authors end the article with pointing to ketamine as a possible treatment for OCD.

The article is reasonably balanced, but at the time it was written, there was no published research on the use of ketamine in people with OCD. A study from 2012 suggests these speculations may have been overly optimistic.

A 2012 research study
I haven’t been able to track down a copy of the full article, so my comments are taken strictly from the abstract. Two of three authors from the IOCDF article are authors on the study. The details are a little unclear but the take-away message is pretty explicit:

“Ketamine effects on OCD symptoms…did not seem to persist or progress after the acute effects of ketamine had dissipated.”

It appears that the effect of ketamine on OCD was very small, and it didn’t last very long. It looks like the enthusiasm in the IOCDF article could use some updating.

Some concluding thoughts
I’d like to be clear that I think the authors of the IOCDF articles are well-intentioned, honest, and excellent researchers. What’s important to keep in mind is that the history of science is littered with ideas that seemed sound or were based on preliminary research, but which were disappointing when studied through controlled research.

As I’ve noted in my other writings on ketamine, I don’t object to ketamine being studied; however, I think researchers should be more cautious about their enthusiasm when talking to the public. Science is a slow progress of trial-and-error, and truly revolutionary treatments are few and far between. Ketamine may yet emerge as useful for depression, but if this study is any indication, its role for OCD doesn’t look very promising.

PTSD involves painful and chronic anxiety and fear following a traumatic experience. People with PTSD often feel like they are reliving the experience through nightmares and flashbacks, may have difficulty sleeping, and may feel detached from themselves and those around them. We’re not sure why some people develop PTSD, but the effects can be devastating. Although we have effective treatments for PTSD, not everyone benefits, so exploring additional options is a noble effort.

The NY Times article reports on an ongoing study of the use of MDMA to treatment people with PTSD. The research is spearheaded by a psychiatrist and nurse couple in South Carolina—Michael and Ann Mithoefer. The couple are aided in their research by the Medical University of South Carolina and funded by The Multidisciplinary Association for Psychedelic Studies.

Initial results from a pilot study were published in the Journal of Psychopharmacology in 2010. You can download the full article here. For the purposes of the blog, I decided to write about published data from this study. While I don’t have any philosophical objection to the rigorous study of recreational drugs, I’m also cautious about making too much of limited studies. Drugs must pass through a variety of rigorous studies and careful analyses before they‘re considered safe enough for the public, and it’s rare that any drug becomes the ‘miracle drug’ often hoped for by the public.

The details of the study

The researchers studied 20 people whom they randomly assigned to receive either MDM-assisted psychotherapy, or the same psychotherapy with an inert placebo. Everyone was assessed two months later to determine if improvements were maintained, and those in the placebo condition were later offered the MDMA-assisted therapy.

Why would a party drug help with PTSD?

The gold standard psychotherapy treatment for PTSD is what’s broadly called exposure therapy. Exposure therapy involves contacting and processing painful reminders of the trauma. However, not everyone benefits from exposure therapy: some people refuse treatment, some become too overwhelmed during treatment, and others are too shut down emotionally to effectively engage.

The authors suggest MDMA may help increase an individual’s willingness to engage painful thoughts and feelings, which may in turn help facilitate successful exposure therapy. While this is a reasonable assumption, theoretically, I do question whether taking a psychedelic drug AND participating in exposure therapy would be less threatening for the majority of people than exposure therapy alone. It might be a hard sell to many people.

What did they do?

The Mithoefers served as the therapists in the study. Participants met with the Mithoefers for a few 90-minute informational sessions. The participants then underwent two sessions lasting 8-10 hours each in which they were administered the MDMA (or placebo). Participants stayed overnight in the clinic after the experimental sessions and were monitored for any medical problems.

Two months after the second experimental session, the researchers followed up with each individual. At that time, they could offer a third MDMA session. Between experimental sessions, participants met for 11 90-minute non-MDMA sessions where they could talk about their experiences following the MDMA sessions.

One thing I was a little uncomfortable with was choice of psychotherapy. Although the authors showed they were familiar with gold standard exposure-based treatment such as prolonged exposure therapy by referencing them in their Introduction, they did not actually use an established treatment. Instead, they created a protocol based on the work of psychiatrist Stanislav Grof, MD, an early advocated of using LSD in psychotherapy. Grof is a controversial figure, regarded as a maverick genius by some and a crackpot by others. Although he continues promote his work, it’s never been tested in rigorous studies.

Referencing gold standard treatments in the intro but basing their treatment on Grof’s work strikes me as a bit of a bait-and-switch.

What did they find?

In brief, people who received MDMA and psychotherapy showed much greater improvement than those who received psychotherapy only. Although there were some side effects from the MDMA, they didn’t appear to be serious and long-lasting. Overall, people seemed to benefit from MDMA-assisted therapy without any major problems.

What I liked about the study

Every study is going to have strengths and weakness, but for a small pilot study, it seemed pretty well done. The measures they used were appropriate and thorough. It appeared they took a number of precautions to ensure the safety of those who participated.

In sum, I thought the design was pretty rigorous, the researchers drew reasonable conclusions about their results, and they acknowledged the problems and limitations with the study. I didn’t see anything sneaky or suspect from what I read.

A few concerns…

Here are some weaknesses of the study. Some are pretty normal and expected, and others are more concerning.

Can you really blind people to a placebo when using a psychedelic drug?

As the authors openly acknowledge, 19 of the 20 participants were able to guess whether they received MDMA or the placebo. This is a common problem in medical research when a drug has strong physical effects. What it means, though, is that it makes it harder to tease out the actual effects from people’s expectations.

For example, as people signed on knowing they might receive MDMA, some may have had greater expectations when they realized they probably received the MDMA; conversely, those in the placebo condition may have been disappointed when they realized they probably didn’t get the MDMA.

MDMA-assisted therapy ain’t cheap!

With 31 hours of contact with two therapists, medical monitoring, and overnight stays in a clinic, MDMA-assisted therapy is going to be much more expensive than basic exposure therapy, which typically involves 10-20 sessions with one therapist for 60-120 minutes.

For these reasons, MDMA-assisted therapy will never be a first line treatment if conducted in this fashion. That said, chronic PTSD is very expensive in the long-term (e.g., meds, inability to work, disability). For people who don’t respond to outpatient treatment, MDMA-assisted may be worth the expense if it helps people who don’t benefit from other approaches.

Why didn’t the researchers adapt a therapy with actual research support?

The authors predicted that MDMA may help individuals more effectively respond to exposure therapy for PTSD. Although the treatment protocol they used contains elements of exposure, it wasn’t based on any gold standard treatments for PTSD.

Instead, they used an invalidated protocol based on the work of Stanislav Grof. This makes me squeamish. Grof’s work has some wonky stuff in it. For example, although this wasn’t included in the protocol, Grof has written that psychological problems occur due to “trauma” during the one’s birth! In his Holotropic Breathwork, people are sometimes encouraged to contact “memories” associated with their births—despite the fact that all science suggests we’re incapable of forming these kinds of memories until around age 2.

This doesn’t mean that all Grof’s ideas are bad, but I have some concern in granting legitimacy to his work given some of the more questionable elements of it.

Concluding thoughts

Despite my concerns, I thought this study was reasonably well-designed and fairly transparent. I think the results are strong enough to warrant continued study of MDMA-assisted therapy for PTSD.

However, I think we’re a long way off from seeing it offered as a treatment to the public. And if it does make it that far, it will likely be a last resort for those who don’t respond to other treatments. If it helps people who don’t find relief for their suffering through other means, however, I’m open to it.

Despite this lack of evidence, a 2007 study found nearly 1 in 4 (21 percent) of individuals who sought treatment for anxiety were prescribed an antipsychotic. Moreover, as Friedman points out, studies are finding that the newer “atypical” drugs have harmful side effects, such as increased cholesterol, movement disorders (e.g., Parkinson’s-like symptoms) and weight gain. Given the increasing numbers of people taking these medications, the risks associated with their use and the lack of research support for many common off-label uses, this is a huge concern.

There have been some articles on the National Public Radio (NPR) website about the use of the drug ketamine as a fast acting treatment for depression (See here and here). Originally developed as an anesthetic, ketamine is better known to the public as the club drug Special K. Beginning with a study published in 2006 from a group of researchers with the National Institute of Health (NIH), ketamine has been explored as possible treatment for depression, and researchers are currently looking for chemically similar alternatives to ketamine with less potential for abuse.

A shortcoming for current antidepressants such as a Prozac is that it usually takes weeks to kick in, and even then, 30-40% of people don’t benefit. By contrast, studies suggest that intravenously-administered (IV) ketamine can improve mood in a matter of hours, and that change appears to last a week or two. For someone who is profoundly depressed and suicidal, this may be a useful alternative to inpatient hospitalization.

Ketamine targets a particular neurotransmitter — glutamate. Current antidepressants more commonly target serotonin, and often dopamine and/or norepinephrine, blocking their reuptake and increasing levels in the brain.

In one of the NPR articles, researcher Dr. Carlos Zarate compares depression to a “leaky faucet in the brain.” Current antidepressants, according to Dr. Zarate, “shut down the water plant,” which means that it a takes a long time for “water to stop flowing through the miles of pipes that eventually lead to the leaky faucet.” Ketamine, he suggests, stops the leaky faucet itself.

Although this metaphor is useful for making the distinction between a fast acting drug and one that takes longer to kick-in, it may also be misleading. The notion that a drug stops the “leaky faucet” of depression at the source sounds very precise and scientific. What may surprise some readers is that our understanding of the biology of depression is still pretty crude.

The Myth of the Chemical Imbalance

Once upon a time, psychiatry had a dream. The sudden introduction of antipsychotics and antidepressants in the 1950’s had a galvanizing effect on the field. It held out the possibility of developing medications that precisely targeted the biological causes of mental health problems.

Decades later, although providers still talk about antidepressants as restoring chemical imbalances, the evidence supporting this view has been pretty disappointing.

For example, although not marketed in the US, there’s an antidepressant called tianeptine that decreases concentrations of serotonin in the brain. Research suggests it’s just as effective as antidepressants that increase concentrations in the brain. This is a bit of a conundrum for the chemical imbalance theory of depression.

Therefore, there’s not a lot of evidence to support the popular notion that antidepressants restore a chemical imbalance. Instead, it’s more accurate to say that antidepressants artificially increase levels of certain neurotransmitters in ways that some people find reduce feelings of depression and anxiety.

Fast Acting Drugs are Not Necessarily Better: The Case of Anxiety

Another thing that concerns me about ketamine is that fast acting drugs are not always a good thing. Case in point: antianxiety medications. No one particularly enjoys feeling anxious. We often want instant relief, or at least something to take the edge off. There’s a class of medications that do just that—benzodiazepines, which including some more commonly known drugs such as Xanax and Ativan. These drugs tend to work pretty quickly, often within 30 minutes.

This finding in itself doesn’t mean the drug is bad. Medications for Parkinson’s disease, which increase dopamine, can also cause schizophrenia-like symptom. (Conversely, long-term use of antipsychotics can cause Parkinsonian-like symptoms in people with schizophrenia.) My point here is that, although researchers have found another potential treatment for depression, it’s unlikely they’ve uncovered the core biological root of depression.

Where Does That Leave Us?

For these reasons, I wince when I hear people talk of “miracle drugs” for psychological problems. It’s not that I see no future for ketamine in depression treatment. It’s more that I found the NPR articles overly optimistic.

As a scientist, I support the continued study of ketamine and related drugs as a potential treatment for depression; however, I’m skeptical about the breadth of its usefulness based on all the other times we’ve gone down this road of “miracle drug” cures. Consequently, although I think ketamine has the potential to be a genuinely new medical approach (i.e., not another minor tweak of an already prescribed antidepressant) to dealing with profound depression, I think we should temper our optimism a bit. The first study on the use of ketamine to treat depression was published in 2006, and the data of if, under what circumstances, and how this drug may be useful are still very much unknown.

It may be, for example, that researchers find ketamine can be useful for people who show up in Emergency Departments suicidally depressed. Rather than sending them to a locked ward, which costs over $1,000 a day, emergency physicians may give them an IV of ketamine. If they respond and mood improves, they can be given an appointment with an outpatient specialist that week and be sent home without further disruption to their lives.

Perhaps this is even how the NIH researchers have conceived of the drug—if so, it wasn’t conveyed in the NPR articles. It seems there is potential for ketamine to be useful in this kind of a scenario, but again, we just don’t have the data yet to know with any certainty. What concerns me is that, based on reports in the media like those on NPR suggesting a “miracle drug” or a “cure,” people may think “I’m depressed—I need some ketamine.” This is a dangerous path where short-term gains could lead to long-term consequences.

PLEASE NOTE: PORTLAND PSYCHOTHERAPY IS NOT INVOLVED IN KETAMINE TREATMENT.

There’ve been some articles on the National Public Radio (NPR) website about the use of the drug ketamine as a fast acting treatment for depression (See here and here). Originally developed as an anesthetic, ketamine is better known to the public as the club drug Special K. Beginning with a study published in 2006 from a group of researchers with the National Institute of Health (NIH), ketamine has been explored as possible treatment for depression, and researchers are currently looking for chemically similar alternatives to ketamine with less potential for abuse.

A shortcoming for current antidepressants such as a Prozac is that it usually takes weeks to kick in, and even then, 30-40% of people don’t benefit. By contrast, studies suggest that intravenously-administered (IV) ketamine can improve mood in a matter of hours, and that change appears to last a week or two. For someone who is profoundly depressed and suicidal, this may be a useful alternative to inpatient hospitalization.

Ketamine targets a particular neurotransmitter glutamate. Current antidepressants more commonly target serotonin, and often dopamine and/or norepinephrine, blocking their reuptake and increasing levels in the brain.

In one of the NPR articles, researcher Dr. Carlos Zarate compares depression to a “leaky faucet in the brain.” Current antidepressants, according to Dr. Zarate, “shut down the water plant,” which means that it a takes a long time for “water to stop flowing through the miles of pipes that eventually lead to the leaky faucet.” Ketamine, he suggests, stops the leaky faucet itself.

Although this metaphor is useful for making the distinction between a fast acting drug and one that takes longer to kick-in, it may also be misleading. The notion that a drug stops the “leaky faucet” of depression at the source sounds very precise and scientific. What may surprise some readers is that our understanding of the biology of depression is still pretty crude.

The Myth of the Chemical Imbalance

Once upon a time, psychiatry had a dream. The sudden introduction of antipsychotics and antidepressants in the 1950’s had a galvanizing effect on the field. It held out the possibility of developing medications that precisely targeted the biological causes of mental health problems.

Decades later, although providers still talk about antidepressants as restoring chemical imbalances, the evidence supporting this view has been pretty disappointing.

For example, although not marketed in the US, there’s an antidepressant called tianeptine that decreases concentrations of serotonin in the brain. Research suggests it’s just as effective as antidepressants that increase concentrations in the brain. This is a bit of a conundrum for the chemical imbalance theory of depression.

Therefore, there’s not a lot of evidence to support the popular notion that antidepressants restore a chemical imbalance. Instead, it’s more accurate to say that antidepressants artificially increase levels of certain neurotransmitters in ways that some people find reduce feelings of depression and anxiety.

Fast Acting Drugs are Not Necessarily Better: The Case of Anxiety

Another thing that concerns me about ketamine is that fast acting drugs are not always a good thing. Case in point: antianxiety medications. No one particularly enjoys feeling anxious. We often want instant relief, or at least something to take the edge off. There’s a class of medications that do just that—benzodiazepines, which including some more commonly known drugs such as Xanax and Ativan. These drugs tend to work pretty quickly, often within 30 minutes.

This finding in itself doesn’t mean the drug is bad. Medications for Parkinson’s disease, which increase dopamine, can also cause schizophrenia-like symptom. (Conversely, long-term use of antipsychotics can cause Parkinsonian-like symptoms in people with schizophrenia.) My point here is that, although researchers have found another potential treatment for depression, it’s unlikely they’ve uncovered the core biological root of depression.

Where Does That Leave Us?

For these reasons, I wince when I hear people talk of “miracle drugs” for psychological problems. It’s not that I see no future for ketamine in depression treatment. It’s more that I found the NPR articles overly optimistic.

As a scientist, I support the continued study of ketamine and related drugs as a potential treatment for depression; however, I’m skeptical about the breadth of its usefulness based on all the other times we’ve gone down this road of “miracle drug” cures. Consequently, although I think ketamine has the potential to be a genuinely new medical approach (i.e., not another minor tweak of an already prescribed antidepressant) to dealing with profound depression, I think we should temper our optimism a bit. The first study on the use of ketamine to treat depression was published in 2006, and the data of if, under what circumstances, and how this drug may be useful are still very much unknown.

It may be, for example, that researchers find ketamine can be useful for people who show up in Emergency Departments suicidally depressed. Rather than sending them to a locked ward, which costs over $1,000 a day, emergency physicians may give them an IV of ketamine. If they respond and mood improves, they can be given an appointment with an outpatient specialist that week and be sent home without further disruption to their lives.

Perhaps this is even how the NIH researchers have conceived of the drug—if so, it wasn’t conveyed in the NPR articles. It seems there is potential for ketamine to be useful in this kind of a scenario, but again, we just don’t have the data yet to know with any certainty. What concerns me is that, based on reports in the media like those on NPR suggesting a “miracle drug” or a “cure,” people may think “I’m depressed—I need some ketamine.” This is a dangerous path where short-term gains could lead to long-term consequences.

Here at Portland Psychotherapy, we spend a lot of time researching the most effective treatments for problems in living. Too often, though, there’s a disconnect between what the research says works and what is often used in practice. Not only is it difficult to educate the public but even mental health professionals can have difficulty keeping up.

For these reasons, I read this CureTogether post (now associated with 23andme.com) with great interest. CureTogether is a website that collects ratings of treatments. It appears to have an ongoing survey of anxiety treatments. Anyone can log in and rate what worked and didn’t work for them. May 13, 2013, the website posted the results from over 10,900 people who had participated in their survey of anxiety treatments.

What do people think works?

I’ll confess: because there’s so much misinformation out there, I was a little worried about what I’d find. I honestly expected to find evidence-practice lagging behind pop psychology. When I saw the actual rankings, however, I thought to myself, “Not bad.”

Cognitive behavior therapy (CBT)—which arguably has the most impressive research base for addressing anxiety disorders—was number 6. Given that CBT is not as “sexy” as other treatments, I was pleasantly surprised to see it in the top 10. Even Acceptance and Commitment Therapy (ACT), the specific branch of CBT offered at Portland Psychotherapy, was number 11. (This is amazing, actually, as ACT is still new to many professionals.) Even exposure therapy, which has the greatest research support but is especially unsexy, was listed at number 14.

More informal treatments such as exercise (#1), yoga (#3), and meditation (#5) also have some research support for being helpful to people. Not everyone needs to see a therapist for anxiety.

What was more concerning—although not surprising—was the prominence of a class of drugs collectively known as benzodiazepines. These include Xanax (#2), Ativan (#8), and Clonazepam (#9). I say “not surprising” because these are commonly prescribed drugs that calm you down within 20-30 minutes. I say “concerning” because, although they make people feel better in the short-term, benzodiazepines can actually maintain anxiety in the long-term: they are a short-term solution, can be addictive, and can lead to withdrawal effects with prolonged use and rebound anxiety when people stop taking it. Xanax, which is faster acting, is particularly dangerous.

What conclusions can we draw?

I should note that this isn’t an objective research study: it’s simply a summary of what people who filled out an online survey say they’ve tried and decided was helpful. That said, it’s an extremely useful snapshot of the real world treatment of anxiety.

What Makes Us Unique

Portland Psychotherapy is a clinic, research & training center with a unique business model that funds scientific research. This results in a team of therapists who are exceptionally well-trained and knowledgeable about their areas of specialty.

Our research lab has dedicated research funding, space, equipment, and staff. We also host postdoctoral fellowships, mentor volunteer research assistants, and provide ongoing training to professionals working in the community.